Experimental evidence from this laboratory has clearly demonstrated that n-butyrate can, in an entirely reversible manner, induce nucleosome histone hyperacetylation in Friend erythroleukemic cells (FLCs) by the inhibition (both "in vivo" and "in vitro") of the histone deacetylase enzymes. Furthermore, we have recently demonstrated by both nucleic acid hybridization studies and by the analysis of "de novo" synthesized cellular proteins by means of two-dimensional gel electrophoresis that n-butyrate also induces new gene expression in treated FLCs and that these effects, too, are reversible. Together these results strongly suggest that histone hyperacetylation (particularly of H3 and H4 to the di-acetylated and higher modified forms) induces new gene activity in these cultured mouse cells. Therefore the aims of the proposed research are: 1) to exlore in detail the possible causal relationship between nucleosome histone hyperacetylation and the initiation of new gene activity in FLCs and try to determine, in as unambiguous a way as possible, whether such a deterministic relationship indeed exists; 2) to determine the generality of the butyrate-induced new gene expression in other types of mouse cells with different states of "determination" or overt "differentiation"; 3) to investigate the possible "in vivo" and "in vitro" regulatory roles of the histone acetyltransferase and deacetylase enzymes in determining the relative levels of histone acetylation in "active" and "inactive" chromatin which, in turn, may be related to the RNA transcriptional activity of the chromatin itself; 4) to investigate the effect of histone hyperacetylation on the "in vitro" template capacity of isolated FLC nuclei (or chromatin) to synthesize 5S ribosomal RNA in response to exogenously supplied, purified, eukaryotic RNA polymerase III; and, 5) to try and isolate genetic mutations in FLCs of the histone deacetylase enzyme genes for detailed biochemical analyses relating to the types of chromatin structure and functional activity in such cells.